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Clinical Activity and Safety of Cabozantinib for Brain Metastases in Patients With Renal Cell Carcinoma
Laure Hirsch1,2, Nieves Martinez Chanza1,3, Subrina Farah4
1Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Importance:
Patients with brain metastases from renal cell carcinoma (RCC) have been underrepresented in clinical trials, and effective systemic therapy is lacking. Cabozantinib shows robust clinical activity in metastatic RCC, but its effect on brain metastases remains unclear.
Objective:
To assess the clinical activity and toxic effects of cabozantinib to treat brain metastases in patients with metastatic RCC.
Design, Setting, And Participants:
This retrospective cohort study included patients with metastatic RCC and brain metastases treated in 15 international institutions (US, Belgium, France, and Spain) between January 2014 and October 2020. Cohort A comprised patients with progressing brain metastases without concomitant brain-directed local therapy, and cohort B comprised patients with stable or progressing brain metastases concomitantly treated by brain-directed local therapy.
Exposures:
Receipt of cabozantinib monotherapy at any line of treatment.
Main Outcomes And Measures:
Intracranial radiological response rate by modified Response Evaluation Criteria in Solid Tumors, version 1.1, and toxic effects of cabozantinib.
Results:
Of the 88 patients with brain metastases from RCC included in the study, 33 (38%) were in cohort A and 55 (62%) were in cohort B; the majority of patients were men (n = 69; 78%), and the median age at cabozantinib initiation was 61 years (range, 34-81 years). Median follow-up was 17 months (range, 2-74 months). The intracranial response rate was 55% (95% CI, 36%-73%) and 47% (95% CI, 33%-61%) in cohorts A and B, respectively. In cohort A, the extracranial response rate was 48% (95% CI, 31%-66%), median time to treatment failure was 8.9 months (95% CI, 5.9-12.3 months), and median overall survival was 15 months (95% CI, 9.0-30.0 months). In cohort B, the extracranial response rate was 38% (95% CI, 25%-52%), time to treatment failure was 9.7 months (95% CI, 6.0-13.2 months), and median overall survival was 16 months (95% CI, 12.0-21.9 months). Cabozantinib was well tolerated, with no unexpected toxic effects or neurological adverse events reported. No treatment-related deaths were observed.
Conclusions And Relevance:
In this cohort study, cabozantinib showed considerable intracranial activity and an acceptable safety profile in patients with RCC and brain metastases. Support of prospective studies evaluating the efficacy of cabozantinib for brain metastases in patients with RCC is critical.
Insights
Cabozantinib demonstrated significant intracranial activity and a good safety profile for treating brain metastases in patients with renal cell carcinoma (RCC). Further prospective studies are recommended to confirm these findings.
Area of Science:
- Oncology
- Nephrology
- Pharmacology
Background:
- Patients with brain metastases from renal cell carcinoma (RCC) are often excluded from clinical trials, leading to a lack of effective systemic therapies.
- Cabozantinib has shown efficacy in metastatic RCC, but its impact on brain metastases is not well-established.
Purpose of the Study:
- To evaluate the clinical activity and safety of cabozantinib in patients with metastatic RCC and brain metastases.
- To assess intracranial response rates and treatment-related toxicities.
Main Methods:
- Retrospective cohort study of 88 patients with metastatic RCC and brain metastases across 15 international institutions.
- Patients were divided into two cohorts: those with progressing brain metastases without local therapy (Cohort A) and those with stable or progressing brain metastases with concomitant local therapy (Cohort B).
- Cabozantinib monotherapy was administered at any treatment line, with intracranial response assessed by RECIST v1.1.
Main Results:
- Intracranial response rates were 55% in Cohort A and 47% in Cohort B.
- Median overall survival was 15 months for Cohort A and 16 months for Cohort B.
- Cabozantinib was well-tolerated, with no unexpected toxicities or treatment-related deaths.
Conclusions:
- Cabozantinib exhibits significant intracranial activity and an acceptable safety profile for treating brain metastases in RCC patients.
- The findings support the need for prospective trials to further validate cabozantinib's efficacy in this patient population.
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